title: Disruption of interstitial cells of Cajal networks after massive small bowel resection.
abstract: OBJECTIVE
  To investigate the disruptions of interstitial cells of Cajal (ICC) in the remaining bowel in rats after massive small bowel resection (mSBR).
  
  
  METHODS
  Thirty male Sprague-Dawley rats fitting entry criteria were divided randomly into three experimental groups (n = 10 each): Group A rats underwent bowel transection and re-anastomosis (sham) and tissue samples were harvested at day 7 post-surgery. Group B and C rats underwent 80% small bowel resection with tissue harvested from Group B rats at day 7 post-surgery, and from Group C rats at day 14 post-surgery. The distribution of ICC at the site of the residual small bowel was evaluated by immunohistochemical analysis of small intestine samples. The ultrastructural changes of ICC in the remnant ileum of model rats 7 and 14 d after mSBR were analyzed by transmission electron microscopy. Intracellular recordings of slow wave oscillations were used to evaluate electrical pacemaking. The protein expression of c-kit, ICC phenotypic markers, and membrane-bound stem cell factor (mSCF) in intestinal smooth muscle of each group were detected by Western blotting.
  
  
  RESULTS
  After mSBR, immunohistochemical analysis indicated that the number of c-kit-positive cells was dramatically decreased in Group B rats compared with sham tissues. Significant ultrastructural changes in ICC with associated smooth muscle hypertrophy were also observed. Disordered spontaneous rhythmic contractions with reduced amplitude (8.5 ± 1.4 mV vs 24.8 ± 1.3 mV, P = 0.037) and increased slow wave frequency (39.5 ± 2.1 cycles/min vs 33.0 ± 1.3 cycles/min, P = 0.044) were found in the residual intestinal smooth muscle 7 d post mSBR. The contractile function and electrical activity of intestinal circular smooth muscle returned to normal levels at 14 d post mSBR (amplitude, 14.9 ± 1.6 mV vs 24.8 ± 1.3 mV; frequency, 30.7 ± 1.7 cycles/min vs 33.0 ± 1.3 cycles/min). The expression of Mscf and c-kit protein was decreased at 7 d (P = 0.026), but gradually returned to normal levels at 14 d. The ICC and associated neural networks were disrupted, which was associated with the phenotype alterations of ICC.
  
  
  CONCLUSIONS
  Massive small bowel resection in rats triggered damage to ICC networks and decreased the number of ICC leading to disordered intestinal rhythmicity. The mSCF/c-kit signaling pathway plays a role in the regulation and maintenance of ICC phenotypes.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Du
authors.forename: Yong-Tao
authors.initials: YT
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D005769:Gastrointestinal Motility; D006984:Hypertrophy; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D007421:Intestine, Small / Q000294:innervation / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: Interstitial cells of Cajal; Intestinal dysfunction; Massive small bowel resection; Slow wave; c-kit